PROJECT SUMMARY/ABSTRACT Childhood obesity is a risk factor for many chronic diseases in childhood and adulthood. Excessive calorie consumption, inadequate physical activity, and genetics are important factors in the burgeoning obesity epidemic; but emerging evidence suggests a role for early-life exposure to air pollution, beginning at the preconception period of gametes maturation and continuing into the entire childhood. Despite that 92% of world?s population today lives in places where ambient air quality exceeds health-based limits per a 2016 WHO report, no published studies have assessed the potential critical time windows, including the preconception period, during which air pollution exposures may adversely affect birth weight and growth trajectory, two significant predictors for childhood obesity. Here we present an overarching hypothesis that air pollution exposures during critical early life developmental periods of preconception, in utero, and first 2 years of life, are associated with obesity-related developmental perturbations, which is manifested by low birth weight and higher growth trajectories during early childhood. We propose to examine this hypothesis in 20,000 newborns whose fathers and mothers have both been enrolled in the Shanghai PreConception Cohort (SPCC) throughout 29 hospitals from year 2016-2018. Each of these newborns has detailed paternal and maternal preconception baseline health, dietary supplement, smoking, alcohol consumption, and demographic data, detailed maternal gestational information, and birth outcome data. During their first 2 years of life, these newborns have up to 6 scheduled physical and health exams, providing data for us to calculate weight and height, potentially non-linear, growth trajectories and assess relevant postnatal variables such as breast-feeding, infection, and illness. Across the 20,000 residence addresses of study subjects, there exist unusually large temporal and spatial variabilities in pollutant concentrations especially for traffic related air pollutants. We will use cutting-edge tempo-spatial exposure models, validated with air monitoring data from 10 governmental stations and our supplementary air pollution measurements, to compute pollutant concentrations at residence addresses for a set of specified time windows including sensitive preconception periods for mothers and fathers (respectively), gestational months and trimesters, and throughout the first 2 years of infancy. By leveraging the rich dataset of this large longitudinal cohort of 20,000 children, we will use distributed lag models to identify critical exposure windows and to examine potential effect differences by factors such as child sex, social economic status and parental smoking status from preconception to gestation periods. If our hypothesis is proven true, this study will provide the first scientific evidence supporting paternal and maternal air pollution exposure during critical time windows, including preconception and in utero periods, as a risk factor for low birth weight and excessive body growth in childhood.